U.S. patent application number 10/553266 was filed with the patent office on 2006-09-14 for transportation of biological matter to a target site in a closed volume for transplantation purposes.
Invention is credited to Avraham Berger, Ben Zion Haim, Avri Hazan, Baruch Meirovich.
Application Number | 20060205999 10/553266 |
Document ID | / |
Family ID | 29215142 |
Filed Date | 2006-09-14 |
United States Patent
Application |
20060205999 |
Kind Code |
A1 |
Berger; Avraham ; et
al. |
September 14, 2006 |
Transportation of biological matter to a target site in a closed
volume for transplantation purposes
Abstract
The present invention is directed toward the transportation of
biological matter to a target site in a closed volume for
transplantation purposes. The present invention involves
provisioning WO99/18872's flattened droplet delivery apparatus with
a pressure sensor for real time monitoring of the prevailing
pressure in its transfer tube for feedback purposes. The present
invention also includes a guide catheter for enabling the
introduction of a delivery catheter to a target site in a closed
volume and concurrent fluid drainage therefrom to discharge
pressure. The present invention also includes a tubing set for use
in a cell therapy procedure.
Inventors: |
Berger; Avraham; (Givataim,
IL) ; Haim; Ben Zion; (Kiryat Ono, IL) ;
Meirovich; Baruch; (Hod Hasharon, IL) ; Hazan;
Avri; (Givataim, IL) |
Correspondence
Address: |
NATH & ASSOCIATES
112 South West Street
Alexandria
VA
22314
US
|
Family ID: |
29215142 |
Appl. No.: |
10/553266 |
Filed: |
April 20, 2003 |
PCT Filed: |
April 20, 2003 |
PCT NO: |
PCT/IL03/00324 |
371 Date: |
October 11, 2005 |
Current U.S.
Class: |
600/34 |
Current CPC
Class: |
A61B 17/435
20130101 |
Class at
Publication: |
600/034 |
International
Class: |
A61B 17/43 20060101
A61B017/43 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 22, 2002 |
US |
10126947 |
Claims
1. Method for transporting biological matter to a target site in a
closed volume for transplantation purposes, the method comprising
the steps of: (a) providing a narrow bore transfer tube having a
proximal end and a distal end and containing a biological matter
bearing culture medium microvolume, the proximal end connected to a
pneumatic system adapted for issuing an outgoing flow of
displacement gas into the transfer tube and drawing an incoming
flow of displacement gas therefrom for respectively displacing the
biological matter bearing culture medium microvolume towards the
distal end and away therefrom; (b) issuing an outgoing flow of
displacement gas for displacing substantially the entire biological
matter bearing culture medium microvolume along the transfer tube
for depositing as a biological matter bearing droplet on a surface
at the target site and controllably blowing miniscule air bubbles
into the biological matter bearing droplet for flattening same on
the surface; and (c) monitoring the prevailing pressure within the
transfer tube during step (b) for providing real time information
with respect to the advancement of the biological matter bearing
culture medium microvolume along the transfer tube and its
successful deposit as a biological matter bearing droplet at the
target site.
2. Method according to claim 1 wherein step (c) includes
graphically displaying the prevailing pressure in the transfer tube
on a monitor.
3. Method according to claim 1 wherein step (c) includes
automatically detecting a fault signature in a pressure waveform
acquired during step (b).
4. Method according to claim 3 wherein step (c) includes
automatically detecting at least one of the following fault
signatures in the pressure waveform: a fault signature FS1
indicative of a pressure drop during an initial outgoing flow of
displacement gas into the transfer tube to displace the biological
matter bearing culture medium microvolume towards its distal end; a
fault signature FS2 indicative of a pressure increase beyond a
predetermined maximum pressure in the transfer tube; and a fault
signature FS3 indicative of a pressure increase after an additional
outgoing pulse of displacement gas to clean the transfer tube's
distal end of any remaining culture medium microvolume.
5. Method according to claim 3 and further comprising step (d) of
automatically issuing a visual and/or aural alarm on detection of a
fault signature in the pressure waveform.
6. Method according to claim 1 and further comprising the steps of:
(e) providing a 2-way valve for selectively connecting the transfer
tube to either an uptake catheter with a distal end selectively
immersible in a biological matter source or a delivery catheter
with a distal end located at the target site; (f) providing a
venting valve for selectively venting the transfer tube's proximal
end to atmospheric pressure; (g) providing a culture medium
microvolume detection device for detecting the presence of a
culture medium microvolume at a predetermined section along the
transfer tube; (h) selectively immersing the uptake catheter's
distal end into the biological matter source and drawing an
incoming flow of displacement gas for aspirating a biological
matter bearing culture medium microvolume into the uptake catheter;
(i) removing the uptake catheter's distal end from the biological
matter source and drawing an incoming flow of displacement gas for
aspirating the biological matter bearing culture medium microvolume
into the transfer tube; (j) venting the transfer tube on detection
of the presence of the biological matter bearing culture medium
microvolume therein; (k) operating the 2-way valve to connect the
transfer tube to the delivery catheter and continuing with step
(b); and (l) repeating steps (h) to (k) to transport a series of
biological matter bearing flattened droplets to the target
site.
7. Method according to claim 6 wherein step (h) includes lifting
the biological matter source relative to the uptake catheter's
distal end for immersing same therein and step (i) includes
lowering the biological matter source for removing the uptake
catheter's distal end therefrom.
8. Method according to claim 6 and further comprising step (m) of
providing a micromanipulator for controlling the location of the
delivery tube's distal end at the target site.
9. Method according to claim 8 and further comprising step (n) of
operating the micromanipulator to gently manipulate the delivery
catheter on detection of a fault signature FS2 in the pressure
waveform.
10. Method according to claim 6 and further comprising step (o) of
operating the pneumatic system to issue a second outgoing pulse of
displacement gas on detection of a fault signature FS3 in the
pressure waveform.
11. Apparatus for transporting biological matter to a target site
in a closed volume for transplantation purposes, the apparatus for
use with a narrow bore transfer tube having a proximal end and a
distal end and containing a biological matter bearing culture
medium microvolume, the apparatus comprising: (a) a pneumatic
system connected to the transfer tube's proximal end and adapted
for issuing an outgoing flow of displacement gas into the transfer
tube and drawing an incoming flow of displacement gas therefrom for
respectively displacing the biological matter bearing culture
medium microvolume towards the transfer tube's distal end and away
therefrom; (b) a control mechanism for controlling the pneumatic
system for issuing an outgoing flow of displacement gas for
discharging substantially the entire biological matter bearing
culture medium microvolume as a biological matter bearing droplet
on a surface at the target site and controllably blowing miniscule
air bubbles into the biological matter bearing droplet for
flattening same on the surface; and (c) a pressure sensor for
monitoring the prevailing pressure within the transfer tube for
providing real time information with respect to the advancement of
the biological matter bearing culture medium microvolume along the
transfer tube and its successful deposit as a biological matter
bearing droplet at the target site.
12. Apparatus according to claim 11 wherein the prevailing pressure
in the transfer tube is graphically displayed on a monitor.
13. Apparatus according to claim 11 and further comprising pattern
recognition functionality for automatically detecting a fault
signature in a pressure waveform monitored during the displacement
of substantially the entire biological matter bearing culture
medium microvolume along the transfer tube and its depositing on
the surface at the target site.
14. Apparatus according to claim 13 wherein the pattern recognition
functionality is capable of automatically detecting at least one of
the following fault signatures in the pressure waveform: a fault
signature FS1 indicative of a pressure drop during an initial
outgoing flow of displacement gas into the transfer tube to
displace the biological matter bearing culture medium microvolume
towards its distal end; a fault signature FS2 indicative of a
pressure increase beyond a predetermined maximum pressure in the
transfer tube; and a fault signature FS3 indicative of a pressure
increase after an additional outgoing pulse of displacement gas for
cleaning the transfer tube's distal end.
15. Apparatus according to claim 13 wherein the pattern recognition
functionality is capable of automatically issuing a visual and/or
aural alarm on detection of a fault signature in the pressure
waveform.
16. Apparatus according to claim 11 and further comprising: (d) a
2-way valve for selectively connecting the transfer tube to either
an uptake catheter with a distal end selectively immersible in a
biological matter source or a delivery catheter with a distal end
located at the target site; (e) a venting valve for selectively
venting the transfer tube's proximal end to atmospheric pressure;
(f) a culture medium microvolume detection device for detecting the
presence of a culture medium microvolume at a predetermined section
along the transfer tube; wherein the control mechanism is
programmed to: i) selectively immerse the uptake catheter's distal
end into the biological matter source and draw an incoming flow of
displacement gas for aspirating a biological matter bearing culture
medium microvolume into the uptake catheter; ii) remove the uptake
catheter's distal end from the biological matter source and draw an
incoming flow of displacement gas for aspirating the biological
matter bearing culture medium microvolume into the transfer tube;
iii) vent the transfer tube on detection of the presence of the
biological matter bearing culture medium microvolume therein; iv)
operate the 2-way valve to connect the transfer tube to the
delivery catheter; v) control the pneumatic system for issuing an
outgoing flow of displacement gas for discharging substantially the
entire biological matter bearing culture medium microvolume as a
biological matter bearing droplet on a surface at the target site
and controllably blowing miniscule air bubbles into the biological
matter bearing droplet for flattening same on the surface; and vi)
repeat steps (i) to (v) to transport a series of biological matter
bearing flattened droplets to the target site.
17. Apparatus according to claim 16 and further comprising a
lifting device for lifting the biological matter source relative to
the uptake catheter's distal end for immersing same therein and
lowering the biological matter source for removing the uptake
catheter's distal end therefrom.
18. Apparatus according to claim 16 and further comprising a
micromanipulator for controlling the location of the delivery
tube's distal end at the target site.
19. Apparatus according to claim 18 wherein the control mechanism
operates the micromanipulator to gently manipulate the delivery
catheter on detection of a fault signature FS2 in the pressure
waveform.
20. Apparatus according to claim 16 wherein the control mechanism
operates the pneumatic system to issue a second outgoing pulse of
displacement gas on detection of a fault signature FS3 in the
pressure waveform.
21. A guide catheter for use with a delivery catheter having an
external diameter D, the guide catheter having a longitudinally
directed lumen with a multitude of longitudinally directed supports
with longitudinally directed inner facing surfaces for slidingly
supported the threading of the delivery catheter through the guide
catheter whereby the longitudinally directed supports assume the
appearance of the spokes of a wheel in a transverse cross sectional
view of the guide catheter with the delivery catheter threaded
therethrough.
22. The catheter according to claim 21 wherein the inner facing
surfaces are curved so as to define an imaginary circle having a
diameter slightly greater than the delivery catheter's external
diameter D.
23. For use with a pneumatic system capable of issuing an outgoing
flow of displacement gas and drawing an incoming flow of
displacement gas, and a biological matter source, a tubing set for
transporting the biological matter from the biological matter
source to a target site in a closed volume for transplantation
purposes, the tubing set comprising a 2-way valve having three
ports, a transfer tube having a proximal end connected to the
pneumatic system and a distal end connected to a first port of the
2-way valve's three ports, an uptake catheter having a proximal end
connected to a second port of the 2-way valve's three ports and a
distal end selectively immersible in the biological matter source,
and a delivery catheter having a proximal end connected to the
third port of the 2-way valve's three ports and a distal end for
location at the target site.
24. The tubing set according to claim 23 wherein the transfer tube
has a tube segment adapted for being hermetically connected to a
pressure sensor for monitoring the prevailing pressure in the
transfer tube.
25. The tubing set according to claim 23 wherein the transfer tube
has a tube segment adapted for being hermetically connected to a
venting valve for venting the transfer tube to atmospheric
pressure.
Description
FIELD OF THE INVENTION
[0001] The invention is in the field of transporting biological
matter to a target site in a closed volume for transplantation
purposes.
BACKGROUND OF THE INVENTION
[0002] In commonly assigned WO99/18872 entitled "Method for
Depositing a Flattened Droplet on a Surface and Apparatus Therefor,
and a Pump Therefor", the contents of which are incorporated herein
by reference, there is illustrated and described a flattened
droplet type IVF-ET procedure in which preferably a single embryo
is accurately deposited on an embryo recipient subject's
endometrium. One advantage of the flattened droplet approach is
that it employs only about 0.3-2 .mu.l culture medium to transport
an embryo to a target site as opposed to 20-40 .mu.l culture medium
in the conventional IVF-ET injection approach but surprisingly,
even this microvolume may increase a typical 3-4 Inches of Water
uterine prevailing pressure by 1-3 Inches of Water. Another
advantage of the flattened droplet approach is that an embryo is
subjected to a far smaller pressure than in comparison to the
conventional IVF-ET injection approach. Clinical trials have
demonstrated that the flattened droplet approach leads to a
considerably higher percentage of successful pregnancies in
comparison to the conventional IVF-ET injection approach. However,
this notwithstanding, the flattened droplet IVF-ET approach still
suffers from technical faults, for example, kinking of a delivery
catheter, blockage of its distal end, and the like, which in all
likelihood lead to an unsuccessful IVF-ET procedure.
SUMMARY OF THE INVENTION
[0003] The present invention is directed toward the transportation
of biological matter to a target site in a closed volume for
transplantation purposes. The present invention involves
provisioning the aforementioned WO99/18872's flattened droplet
delivery apparatus with a pressure sensor for real time monitoring
of the prevailing pressure in its transfer tube. The prevailing
pressure can be displayed on a monitor particularly during the
actual transfer of an embryo bearing culture medium microvolume to
an embryo recipient subject's endometrium such that an occurrence
of one or more of the aforelisted technical faults would be
immediately apparent to a trained practitioner who may then take
appropriate corrective action. Pattern recognition functionality
can be readily applied to a pressure waveform of the prevailing
pressure within a transfer tube for detecting an occurrence of one
or more of the aforelisted technical faults by virtue of each
technical fault having a uniquely identifiable fault signature,
thereby enabling the automatic issuance of a visual and/or aural
alarm in the case of such an occurrence. To largely negate the
aforesaid typical 1-3 Inches of Water prevailing uterine pressure
increase during a flattened droplet type IVF-ET procedure, the
delivery catheter for delivering the embryo bearing culture medium
microvolume to an embryo recipient subject's uterus is preferably
introduced through an extruded guide catheter designed to slidingly
support the threading of the delivery catheter therethrough, and
enable concurrent fluid drainage from her uterus to lower her
prevailing uterine pressure.
[0004] The present invention also enables the transportation of a
series of biological matter bearing flattened droplets for
effecting cell based therapy procedures rather than the presently
suggested injection approach as described in an on-line article
entitled "Stem Cells: A primer" as retrieved from the National
Institute of Health (NIH)'s website on Apr. 12, 2003 <URL:
[0005] www.nih.gov/news/stemcell/primer.htm>. Cell based
therapies are now being hypothesized to treat a wide range of
diseases including inter alia Parkinson's disease, diabetes,
traumatic spinal cord injury, heart disease, vision and hearing
loss, and the like. In this context, biological matter may be in
the form of complete cells, for example, stem cells, germ cells,
and the like, and also cell components, for example, DNA, RNA, and
the like. It is believed that the flattened droplet approach in
comparison to the conventional injection approach will be
particularly advantageous for cell based therapy procedures by
virtue of the fact that the aforesaid advantages of the former
approach will be even more beneficial due to cell based therapy
procedures requiring the transplantation of far greater quantities
of biological matter than preferably a single embryo for an IVF-ET
procedure, and the target sites of cell based therapy procedures
are in closed volumes far smaller than a human uterus and therefore
more susceptible to increases in prevailing pressures.
BRIEF DESCRIPTION OF DRAWINGS
[0006] In order to understand the invention and to see how it may
be carried out in practice, preferred embodiments will now be
described, by way of non-limiting examples only, with reference to
the accompanying drawings, in which:
[0007] FIG. 1 is a pictorial representation of apparatus for
effecting a flattened droplet type IVF-ET procedure in accordance
with the present invention;
[0008] FIG. 2 is a transverse cross section view of a guide
catheter with a delivery catheter threaded therethrough for use in
a flattened droplet type IVF-ET procedure;
[0009] FIGS. 3A-3F are pictorial representations showing the
transport of an embryo bearing culture medium microvolume to an
embryo recipient subject's endometrium during a flattened droplet
type IVF-ET procedure;
[0010] FIG. 4 is a graph showing the pressure waveform of the
prevailing pressure in the transfer tube of the apparatus of FIG. 1
during a flattened droplet type IVF-ET procedure together with
fault signatures of three potential technical faults which may
occur during such a procedure;
[0011] FIG. 5 is a pictorial representation of apparatus for
transporting biological matter for a cell based therapy procedure
in accordance with the present invention;
[0012] FIGS. 6A to 6C are pictorial representations showing the
operation of the apparatus of FIG. 5;
[0013] FIG. 7 is a graph showing the prevailing pressure within the
transfer tube of the apparatus of FIG. 5 during a cell based
therapy procedure; and
[0014] FIG. 8 is a pictorial representation showing the fusing
together of a number of stem cell bearing flattened droplets into a
large drop.
DESCRIPTION OF PREFERRED EMBODIMENTS
[0015] FIG. 1 shows apparatus 1 for effecting an improved flattened
droplet type IVF-ET procedure. Apparatus 1 includes a suction
control unit 2 typically permanently located in a laboratory for
the preparation of an embryo bearing delivery catheter
(constituting a narrow bore transfer tube) 3, a transfer control
unit 4 typically permanently located in a treatment room where
IVF-ET procedures are carried out and a portable casing 6 for
consecutive connection to the suction control unit 2 and the
transfer control unit 4 by means of connectors 7 and 8. Insertion
of the delivery catheter 3 into an embryo recipient subject's
uterus is preferably through an extruded guide catheter 9 having,
say, four to eight, longitudinally directed supports 11 whose
longitudinally directed curved inner facing surfaces 12 define an
imaginary circular in the transverse cross section view of FIG. 2
with a diameter slightly larger than the delivery catheter's
diameter D whereby the delivery catheter 3 can be readily slidingly
threaded therethough. The use of the guide catheter 9 enables fluid
drainage from an embryo recipient subject's uterus to avoid a
significant increase in her uterine pressure which may militate
against a successful IVF-ET procedure.
[0016] The casing 6 includes a pneumatic system 13 which is
permanently connected to the delivery catheter 3 during an entire
IVF-ET procedure via suitable air tubing 14, and a receptacle 16
for accommodating the delivery catheter 3 during the transport of
the casing 6 from a laboratory to a treatment room. The pneumatic
system 13 includes a microvolume pump (not shown), for example, as
described with reference to WO99/18872's FIGS. 3-5, and a pressure
sensor 17 for monitoring the prevailing pressure within the
delivery catheter 3 for display as a Single Flattened Droplet
Pressure Waveform (SFDPW) on a computer 18. The pressure sensor 17
is operative over 0-1 psi a pressure range and has an about .+-.1%
pressure sensitivity. IC Sensor's Model 1210 pressure sensor would
be suitable for use as pressure sensor 17. The computer 18 can be
programmed with pattern recognition functionality 19 to
automatically issue visual and/or aural alarms on detection of an
occurrence of one or more fault signatures in the SFDPW as
described hereinbelow with reference to FIG. 4.
[0017] The pneumatic system 13 is under the control of a control
mechanism 21 including a control pad 22 for controlling the suction
control unit 2 for initiating a user controlled suction mode to
load the delivery catheter 3 with an embryo bearing culture medium
microvolume and a foot pedal 23 for controlling the transfer
control unit 4 for initiating a user initiated automated delivery
mode for depositing an embryo bearing flattened droplet on an
embryo recipient subject's endometrium. The control pad 22 has an
upstroke control 22A for drawing an incoming flow of displacement
gas into the pneumatic system 13 from the delivery catheter 3, a
downstroke control 22B for issuing an outgoing flow of displacement
gas from the pneumatic system 13 into the delivery catheter 3, and
optionally a speed control 22C for controlling the flow rate of the
displacement gas either from or into the delivery catheter 3. The
suction control unit 2 is also provided with a reset button 26 for
priming the pneumatic system 13 for a pre-suction mode of issuing
an outgoing flow of displacement gas as indicated by a READY
indicator light 27 prior to the loading of the delivery catheter 3.
The different stages of the automatic delivery mode are indicated
by a READY indicator light 28, a GO indicator light 29 and a DONE
indicator light 31.
[0018] For the sake of conciseness, the loading of the delivery
catheter 3 with one or more embryo(s) in accordance with the
procedure described with reference to WO99/18872's FIGS. 2A-2E is
not repeated here. The depositing of an embryo bearing flattened
droplet on an embryo recipient subject's endometrium S is now
described with reference to the steps shown in FIGS. 3A-3F and
SFDPW shown in FIG. 4.
[0019] The delivery catheter's distal end 3A is laid on an embryo
recipient subject's endometrium S (see FIG. 3A) whereupon a first
depression on the foot pedal 23 causes the READY indicator light 28
to be lit indicating that the automatic delivery mode can be
initiated. Thereafter, a second depression on the foot pedal 23
causes the GO indicator light 29 to be lit indicating that an
outgoing flow of displacement gas is displacing the embryo bearing
culture medium microvolume towards the distal end 3A (see FIG. 3B).
The outgoing flow of displacement gas causes a concave shaped
meniscus to be slowly formed which increases in size until it
suddenly ruptures whereby most of the embryo bearing culture medium
microvolume is discharged as a droplet D on the surface S (see
FIGS. 3C and 3D). The discharge is accompanied by blowing miniscule
air bubbles B into the droplet D for frothing it and thereby
considerably widening its projected surface area on the embryo
recipient subject's endometrium S to form the flattened droplet F
whose shape is maintained by its prevailing surface tension with
the embryo recipient subject's endometrium S (see FIG. 3E).
[0020] The GO indicator light 29 is then extinguished indicating
that the practitioner should slightly withdraw the delivery
catheter 3 so as to detach its distal end 3A from the droplet F
whilst at the same time there is a slow discharge of displacement
gas. Withdrawal is limited to between about 10-15 mm such that the
distal end 3A still lies along the embryo recipient subject's
endometrium S. And finally, a further outgoing pulse of
displacement gas is provided to clean the distal end 3A of any
remaining culture medium (see FIG. 3F). The DONE indicator light 31
is then lit to indicate that the delivery catheter 3 can be
completely removed from the embryo recipient subject's uterus.
[0021] FIG. 4 also shows three fault signatures FS1, FS2 and FS3
superimposed on the SFDPW of technical faults which may occur
during a flattened droplet type IVF-ET procedure as follows:
[0022] A fault signature FS1 appears as a pressure drop at the
beginning of the SFDPW during an initial issue of outgoing flow of
displacement gas to outwardly displace the embryo bearing culture
medium microvolume along the delivery catheter 3. A fault signature
FS1 is indicative that the pneumatic system 13 is not hermetically
sealed and that suitable action be taken to hermetically seal the
pneumatic system 13 before a flattened droplet type IF-ET procedure
can be continued.
[0023] A fault signature FS2 appears as a pressure increase beyond
a predetermined maximum pressure, say, 12 Inches of Water for an
IVF-ET procedure. A fault signature FS2 is indicative of either a
kink along the delivery catheter 3 or a blockage at its distal end
3A due to soft tissue or blood. A fault signature FS2 requires that
a practitioner attempt to unkink the delivery catheter 3 or unblock
its distal end 3A by gently manipulate the delivery catheter 3 to
and fro or up and down.
[0024] A fault signature FS3 appears as a pressure increase towards
the end of the SFDPW after the issue of the further outgoing pulse
of displacement gas denoted 3F in FIG. 4. The pressure increase
appears instead of the prevailing pressure in the delivery catheter
3 dropping down to a typical uterine prevailing pressure of about
3-4 Inches of Water. A fault signature FS3 is indicative of the
back flow of a flattened droplet F possibly including the embryo E
into the delivery catheter 3. A fault signature FS3 requires that a
practitioner issue a second outgoing pulse of displacement gas.
[0025] FIG. 5 shows apparatus 51 for automatically transporting a
series of biological matter bearing flattened droplets to a target
site for, say, a stem cell therapy procedure. The apparatus 51
includes a pneumatic system 52 under the control of a computer
(constituting a control mechanism) 53 including the pattern
recognition functionality 19 programmed for detecting the fault
signatures FS1, FS2 and FS3, and issuing suitable alarms, and a
tubing set 54 designed for single or multiple use. The pneumatic
system 52 includes a microvolume pump 56, for example, as described
with reference to WO99/18872's FIGS. 3-5.
[0026] The tubing set 54 includes a transfer tube 57 having a
proximal end 57A, a distal end 57B, and a pair of tube segments 57C
and 57D; a two-way valve 58 under the control of the computer 53
and having three ports 58A, 58B and 58C; an uptake catheter 59
having a proximal end 59A and a distal end 59B; and a delivery
catheter 61 having a proximal end 61A and a distal end 61B. The
prevailing pressure in the transfer tube 57 is monitored by a
pressure sensor 62 hermetically connected to the tube segment 57C
and connected to the computer 53 for real time feedback purposes
and for displaying a Multiple Flattened Droplet Pressure Waveform
(MFDPW) arising from a stem cell therapy procedure. The transfer
tube 57 can be selectively vented to atmospheric pressure P.sub.0
by a normally closed (NC) venting valve 63 hermetically connected
to the tube segment 57D and under the control of the computer
53.
[0027] The computer 53 also receives closed loop feedback from an
electro-optical culture medium microvolume detection device 64 for
detecting the presence of a stem cell bearing culture medium
microvolume within a predetermined segment of the transfer tube 54.
The computer 53 also controls a lifting device 66 for controlling
the height of a source of stem cells 67 for selectively immersing
the uptake catheter's distal end 59B therein, and a
micromanipulator 68 for controlling the location of the delivery
catheter's distal end 61B.
[0028] Operation of apparatus 51 for transplanting a single stem
cell bearing flattened droplet at the target site is now described
with reference to FIGS. 6A-6C is as follows:
[0029] The computer 53 sets the 2-way valve 58 to connect the
uptake catheter 59 to the microvolume pump 56, operates the lifting
device 66 to lift the stem cell source 67 to immerse the uptake
catheter's distal end 59B therein, controls the microvolume pump 56
for drawing an incoming flow of displacement gas thereinto so as to
aspirate a stem cell bearing culture medium microvolume into the
uptake catheter 59, and then operates the lifting device 66 a
second time to lower the stem cell source 67 to remove the distal
end 59B therefrom (see FIG. 6A).
[0030] The computer 53 continues to operate the microvolume pump 56
to draw an incoming flow of displacement gas thereinto to aspirate
the stem cell bearing culture medium microvolume into the transfer
tube 57 towards its proximal end 57A. Upon its reaching the culture
medium microvolume detection device 64, the culture medium
microvolume detection device 64 sends a signal to the computer 53
which interrupts the operation of the microvolume pump 56 and opens
the NC venting valve 63 to stop the inward movement of the stem
cell bearing culture medium microvolume (see FIG. 6B).
[0031] The computer 53 closes the NC venting valve 63, sets the
2-way valve 58 to connect the transfer tube 57 to the delivery
catheter 61, and operates the microvolume pump 56 to issue an
outgoing flow of displacement gas to outwardly displace the stem
cell bearing culture medium microvolume towards the distal end 61B
(see FIG. 6C). The computer 53 operates the microvolume pump 56 to
deposit a stem cell bearing flattened droplet at the target site in
a similar manner as described hereinabove with respect to the
flattened droplet type IVF-ET procedure.
[0032] The computer 53 operates the micromanipulator 68 to withdraw
the delivery catheter's distal end 61B by about 0.5-3 mm to detach
a stem cell bearing flattened droplet therefrom. The computer 53
also operates the micromanipulator 68 to gently manipulate the
delivery catheter 61 on detection of a fault signature FS2 and the
microvolume pump 56 on detection of a fault signature FS3.
[0033] FIG. 7 shows a Multiple Flattened Droplet Pressure Waveform
(MFDPW) corresponding to the transportation of successive stem cell
bearing flattened droplets to a target site. The MFDPW has a
stepped appearance reflecting the fact that each transplantation of
a stem cell flattened droplet at the target site increases the
volume thereat which in turn increases the prevailing pressure in
the transfer tube 57 required to deposit the next flattened
droplet. The MFDPW is effectively constituted by a series of SFDPWs
(see FIG. 4) except with an additional sub-atmospheric pressure
segment between each pair of consecutive SFDPWs. The
sub-atmospheric pressure segments each correspond to the loading of
the uptake catheter 59 with a stem cell culture medium microvolume
and thereafter its inward displacement to the transfer tube 57.
[0034] FIG. 8 shows that stem cell bearing flattened droplets D
tend to fuse into a single large drop L if deposited sufficiently
adjacent to one another at the target site.
[0035] Various modifications and changes may be made in the
configuration described hereinabove that come within the spirit of
the invention. The invention embraces all such changes and
modifications coming within the scope of the appended claims.
* * * * *
References